Antisense-mediated downregulation of anti-apoptotic proteins induces apoptosis and sensitizes head and neck squamous cell carcinoma cells to chemotherapy

Sharma, Himani; Singh, Narinderbir

doi:10.1016/s1359-6349(06)80555-0

Cited by 23 publications

(28 citation statements)

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“…However, resistant subline exerted increased Bcl-2, survivin and c-IAP-1 levels accompanied by a marked decrease of p53 in all treatments. This corresponded to several findings, when Bcl-2 and Bcl-xl [27,28,29] protein over-expression is often, but not always [29], associated with CDDP resistance, and when Bcl-2 or Bcl-xl antagonists augmented CDDP efficacy [31,32]. In parental human bladder cancer cells, in response to CDDP, up-regulation of Bax was time-dependent and resulted in apoptosis.…”

Section: Discussionsupporting

confidence: 82%

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Duraj¹,

Hunáková²,

Bodo³

et al. 2009

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Section: Discussionsupporting

confidence: 82%

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Duraj¹,

Hunáková²,

Bodo³

et al. 2009

neo

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“…The overexpression of antiapoptotic members of the Bcl-2 protein family, including Bcl-X L and Bcl-2, appears to play an important role in conferring apoptosis resistance in HNSCC (4,5). Bcl-X L and Bcl-2 are known to inhibit apoptosis by binding and neutralizing the activities of proapoptotic members of the Bcl-2 protein family, including the multidomain proteins Bax and Bak and the BH3 domain -only proteins Bim, Bik, Noxa, and Puma (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of Bcl-2 is also common in HNSCC, albeit to a somewhat lesser degree (8). Antisensemediated down-regulation of Bcl-X L and Bcl-2 in HNSCC cell lines has been shown to promote apoptosis and sensitize these cells to cisplatin and etoposide (5). Similarly, molecular targeting of Bcl-X L and Bcl-2 with the smallmolecule inhibitor (-)-gossypol (9 -11) or short peptides derived from the BH3 domains of proapoptotic proteins (12) promotes apoptosis and chemosensitivity in HNSCC cells.…”

Section: Introductionmentioning

confidence: 99%

Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells

Grandis

et al. 2008

Molecular Cancer Therapeutics

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“…It is noteworthy that Bcl-X L overexpression correlates with chemotherapy resistance in patients with HNSCC (Trask et al, 2002). Antisense-mediated down-regulation of Bcl-X L and Bcl-2 has been shown to sensitize HNSCC cell lines to chemotherapy-induced apoptosis (Sharma et al, 2005). Bcl-X L and Bcl-2 inhibit chemotherapy-induced apoptosis by binding and sequestering proapoptotic members of the Bcl-2 protein family (Danial and Korsmeyer, 2004).…”

mentioning

confidence: 99%

ABT-737 Synergizes with Chemotherapy to Kill Head and Neck Squamous Cell Carcinoma Cells via a Noxa-Mediated Pathway

Zang²,

Li³

et al. 2009

Mol Pharmacol

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Overexpression of Bcl-X L , an antiapoptotic Bcl-2 family member, occurs in a majority of head and neck squamous cell carcinomas (HNSCCs) and correlates with chemotherapy resistance in this disease. Overexpression of Bcl-2 is also observed in HNSCC, albeit less frequently. We have previously shown that peptides derived from the BH3 domains of proapoptotic proteins can be used to target Bcl-X L and Bcl-2 in HNSCC cells, promoting apoptosis. In this report, we examined the impact of ABT-737 (for structure, see Nature 435:677-681, 2005), a potent small-molecule inhibitor of Bcl-X L and Bcl-2, on HNSCC cells. As a single agent, ABT-737 was largely ineffective at promoting HNSCC cell death. By contrast, ABT-737 strongly synergized with the chemotherapy drugs cisplatin and etoposide to promote HNSCC cell death and loss of clonogenic survival. Synergism between ABT-737 and chemotherapy was associated with synergistic activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. Treatment with ABT-737 plus chemotherapy resulted in dramatic up-regulation of proapoptotic Noxa protein, and small interfering RNA (siRNA)-mediated inhibition of Noxa up-regulation partially attenuated cell death by the synergistic combination. Treatment with cisplatin or etoposide, alone or in combination with ABT-737, resulted in substantial down-regulation of Mcl-1L, a known inhibitor of ABT-737 action. Further down-regulation of Mcl-1L using siRNA failed to enhance killing by the cisplatin/ABT-737 synergistic combination, indicating that chemotherapy treatment of HNSCC cells is sufficient to remove this impediment to ABT-737. Together, our results demonstrate potent synergy between ABT-737 and chemotherapy drugs in the killing of HNSCC cells and reveal an important role for Noxa in mediating synergism by these agents.

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Antisense-mediated downregulation of anti-apoptotic proteins induces apoptosis and sensitizes head and neck squamous cell carcinoma cells to chemotherapy

Cited by 23 publications

References 0 publications

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Administration of isothiocyanate (E-4IB) and cisplatin leads to altered signalling and lysosomal export in human ovarian carcinoma sensitive- and cisplatin-resistant cells

Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells

ABT-737 Synergizes with Chemotherapy to Kill Head and Neck Squamous Cell Carcinoma Cells via a Noxa-Mediated Pathway

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